Aminoglycosides (AMGs) are an important class of antibiotics, which are active against a broad rage of difficult to treat bacterial infections. AMGs are particularly useful for the treatment of serious Gram-negative infections resulting from Pseudomonas aeruginosa. AMG resistance in P. aeruginosa continues to grow at an alarming rate and there is an immediate need to develop new AMGs against drug-resistant strains. In the past, the difficulty of complex carbohydrate synthesis has limited the ability of medicinal chemists to develop AMGs with these improved properties. We plan to use our complex carbohydrate synthesis platform, OPopSTM, to tackle the medicinal chemistry of AMGs. The long-term objectives of this program are to identify and develop a novel broad-spectrum AMG, active against drug-resistant bacteria and to develop an AMG with an improved safety profile relative to the currently available alternatives using OPopSTM technology. Furthermore, we believe the OPopSTM platform will be a valuable toot to study carbohydratebased medicinal chemistry in a host of other disease areas. Broadly, the specific aims of our program are to: i) Design efficient syntheses for large numbers of AMG antibiotics, which incorporate Optimer's OPopSTM carbohydrate synthesis technology. ii) Synthesize large numbers of novel AMGs. iii) Screen the resulting AMGs against panels of bacteria including drug-resistant strains of P. aeruginosa, Enterococci sp., E.coli, and S. aureus. iv) Identify a few promising lead compounds for advancement into in vivo efficacy studies, safety studies and ultimately clinical development.